DESCRIPTION: The parent grant (CA43315-09) deals with the synthesis of antiviral compounds targeted to the V3 loop, the definition of their structure-function relationships, assessment of their antiviral activity against primary HIV-1 isolates, and the design of compounds with reactive groups leading to irreversible binding to gp120/41. The proposed FIRCA aims are the synthesis of (a) new porphyrin derivatives, (b) phosphorothioate cytosine oligonucleotides with various pentofuranosyl configurations and phosphonate cytosine oligonucleotides with hydrophobic functional groups inserted in the vicinity of the phosphonate moieties, and (c) conjugates of the porphyrin derivatives and oligonucleotides. The in vitro testing of the synthesized molecules for anti-HIV effect and their binding to gp120 and the V3 loop will be done as part of the parent grant. The foreign collaborator (principal investigator) is Dr. Ivan Rosenberg of the Institute of Organic Chemistry and Biochemistry in Prague, assisted by Drs. Tocik, Liboska and Endova.